Genetic Variation for Enzyme in Lung May Point to Cancer Susceptibility Gene, Mechanisms That May Cause Cancer

A preliminary study by scientists at the National Institute of Environmental Health Sciences indicates that a human gene variation that reduces production of an enzyme in the lungs also makes people less susceptible to lung cancer.

The scientists said about 8 percent of the population -- 9.4 percent of African Americans and 7.8 percent of Caucasians--have the "protective" gene form, or polymorphism, which reduces by about 54 percent the risk of a smoker getting lung cancer. Called the myeloperoxidase gene, the protective form of it is designated A/A. Most people have the A/G or G/G forms of the gene which confer no protection against lung cancer.

Only about 5%, or 16 out of 339, of people in the study with lung cancer had the protective gene, but about 8%, 59 out of 703, of controls had it.

NIEHS' Stephanie J. London, M.D., Dr.P.H., and Jack A. Taylor, M.D., and BioServe Biotechnologies' Terri A. Lehman, reported today in Cancer Research that they collected blood samples from lung cancer patients and randomly collected non-patient controls from Los Angeles County, Calif., which were then compared for the presence of genotype A/A.

The significance of the presence or absence of genotype A/A, and its consequences for a person's chances of developing lung cancer, is related to the enzyme which is produced by everyone but reduced in people with genotype A/A.

"The enzyme, myeloperoxidase, activates the potent carcinogen benzo(a)pyrene, which is a product of tobacco smoke, the burning of most fuels and most other kinds of combustion," Dr. London said.

She said the enzyme may also lead to lung cancer by generating free radicals which are molecules that disrupt the copying of genes and cause genetic errors that can lead to cancer.

"This is a preliminary study; it requires confirmation in other data. If confirmed these potential mechanisms will have to be studied more fully," Dr. London said. "Myeloperoxidase is of interest -- there is a lot of it in the lungs of smokers and it is good at activating tobacco carcinogens into their more dangerous forms."

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